1. Field of the Invention
The present invention is in the field of steroid chemistry. More particularly, it concerns the stereoisomerically pure 17.alpha.-ethynyl-estra-2-en-17.beta.-ol, its 17.beta.-hydroxy esters, and their preparation and use in the control of female fertility in mammals, particularly female human beings. These compounds have antiprogestational activity.
2. Related Art
The use of substituted steroids for the control of conception in female mammals has been known for some time, see for example, G. Pincus et al. in Science, Vol. 124, p. 890 (1956); J. Rock et al. in Science, Vol. 124, p. 891 ff (1956); G. Pincus, The Control of Fertility, Academic Press, New York, New York, published in 1965; and C. Djerassi, Science, Vol. 151, p. 3716 (1966).
17.alpha.-Ethynyl-estra-2-en-17.beta.-ol is a known compound See, A. Bowers et al., in Steroids, Vol. 6, pp. 156 to 161 (1963). In practice as shown herein, the synthetic route described by Bowers et al. produces a mixture of 17.beta.-hydroxy compounds, i.e. the .DELTA..sup.2 and .DELTA..sup.3 isomers. A pure isomer is not produced. Further, no biological data is presented for the effect of this compound in a mammalian system. Bowers et al. show that these products have androgenic effects, but the reference does not disclose their use for fertility control in females.
In U.S. Pat. No. 3,624,203, Overbeek discloses compounds of the formula: ##STR2## in which
R.sub.1 is H or an acyl group or an alkyl group;
R.sub.2 is an alkyne group of two to four carbon atoms; and in which there is
one ethylenic bond connecting carbon atom five with carbon atom four or carbon atom six.
The series of compounds described by Overbeek are useful as oral contraceptives for females. These steroid structures are different from the ones described herein. In other words, all of compounds described by Overbeek have either a carbon-carbon double bond at C(4)-C(5) or C(5) to C(6), rather than at C(2) to C(3) as in the compounds of the present invention.
In U.S. Pat. No. 4,278,668, Gueritee discloses compounds of the formula: ##STR3## in which R is hydrogen or an acetyl group. These compounds are effective in the treatment of endometriosis (the presence of uterus mucous membrane lining tissue in abnormal locations, including the uterine wall, ovaries, or extragenital sites). The Gueritee compounds possess a 19-methyl group whereas the compounds of interest described herein do not have a 19-methyl group (i.e. the 19-nor-derivative).
In U.S. Pat. No. 3,875,188, Galantay disclosed 17.alpha.-(lower alkyl) allenyl steroids of the general formula: ##STR4## wherein:
R.sup.1 is alkyl of 1 to 3 carbon atoms;
R.sup.2 is hydrogen, or lower alkanoyl having 2 to 4 carbon atoms;
R.sup.3 is alkyl having 1 to 3 carbon atoms;
R.sup.4 is hydrogen, hydroxy or lower alkynoyloxy; and
Z embracing rings A and B has a number of substituents. These compounds are useful as fertility control agents in animals. However, none of these allenyl steroids are disclosed in the present invention.
In British Patent No. 919,565, is disclosed the preparation of 17.alpha.-chloroethynyl steroid derivatives which have hormonal properties, including oestrogenic, progestational, ovulation-inhibiting and claudogenic antifertility properties. Unsaturated derivatives including a .DELTA..sup.2 -isomer are disclosed. However, no disclosure is made concerning the 17.alpha.-ethynyl-17.beta.-hydroxy steroids or the 17.beta.-acyloxy compounds of the present invention.
British Patent No. 961,502 discloses a number of 17.alpha.-butadynyl-17.beta.-hydroxy steroids. The compounds have useful oestrogenic and claudogenic properties. However, none of the compounds or intermediates disclosed is 17.alpha.-ethynyl-estra-2-en-17.beta.-ol or its 17.beta.-esters.
The present invention concerns a group of steroid compounds having antiprogestational activity which are useful in the control of fertility in female mammals.